Effect of Drug Disposal Kits and Fact Sheets on Elimination of Leftover Prescription Opioids: The DISPOSE Multi-Arm Randomized Controlled Trial.

OBJECTIVE: To determine how passively providing informational handouts and/or drug disposal kits affects rates of leftover prescription opioid disposal. DESIGN: A multi-arm parallel-group randomized controlled trial with masked outcome assessment and computer-guided randomization. SETTING: Johns Hopkins Health System outpatient pharmacies. SUBJECTS: Individuals who filled ≥1 short-term prescription for an immediate-release opioid for themselves or a family member. METHODS: In June 2019, 499 individuals were randomized to receive an informational handout detailing U.S. Food and Drug Administration-recommended ways to properly dispose of leftover opioids (n = 188), the informational handout and a drug disposal kit with instructions on its use (n = 170), or no intervention (n = 141) at prescription pickup. Subjects were subsequently contacted by telephone, and outcomes were assessed by a standardized survey. The primary outcome was the use of a safe opioid disposal method. RESULTS: By 6 weeks after prescription pickup, 227 eligible individuals reported they had stopped taking prescription opioids to treat pain and had leftover medication. No difference in safe disposal was observed between the non-intervention group (10% [6/63]) and the group that received disposal kits (14% [10/73]) (risk ratio = 1.44; 95% confidence interval: 0.55 to 3.74) or the group that received a fact sheet (11% [10/91]) (risk ratio = 1.15; 95% confidence interval: 0.44 to 3.01). CONCLUSIONS: These findings suggest that passive provision of a drug disposal kit at prescription pickup did not increase rates of leftover opioid disposal when compared with provision of a fact sheet alone or no intervention. Active interventions may deserve further investigation.

Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

Association of goals of care meetings for hospitalized cancer patients at risk for critical care with patient outcomes.

BACKGROUND: Caring for cancer patients with advanced and refractory disease requires communication about care preferences, particularly when patients become ill enough to be at risk for critical care interventions potentially inconsistent with their preferences. AIM: To describe the use of goals of care discussions in patients with advanced/refractory cancer at risk for critical care interventions and evaluate associations between these discussions and outcomes. DESIGN: Cohort study describing patients/families' perceptions of goals of care meetings and comparing health care utilization outcomes of patients who did and did not have discussions. SETTING/PARTICIPANTS: Inpatient units of an academic cancer center. Included patients had metastatic solid tumors or relapsed/refractory lymphoma or leukemia and were at risk for critical care, defined as requiring supplemental oxygen and/or cardiac monitor. RESULTS: Of 86 patients enrolled, 34 (39%) had a reported goals of care discussion (study group). Patients/families reported their needs and goals were addressed moderately to quite a bit during the meetings. Patients in the study group were less likely to receive critical care (0% vs 22%, p = 0.003) and more likely to be discharged to hospice (48% vs 30%, p = 0.04) than the control group. Only one patient in the study group died during the index hospitalization (on comfort care) (3%) compared with 9(17%) in the control group (p = 0.08). CONCLUSION: Goals of care meetings for advanced/refractory cancer inpatients at risk for critical care interventions can address patient and family goals and needs and improve health care utilization. These meetings should be part of routine care for these patients.

Operationalizing the new DEA exception: A novel process for dispensing of methadone for opioid use disorder at discharge from acute care settings.

PURPOSE: To describe one strategy for dispensing of methadone at emergency department (ED) and hospital discharge implemented within 2 urban academic medical centers. SUMMARY: Expanding access to medications for opioid use disorder (OUD) is a national priority. ED visits and hospitalizations offer an opportunity to initiate or continue these lifesaving medications, including methadone and buprenorphine. However, federal regulations governing methadone treatment and significant gaps in treatment availability have made continuing methadone upon ED or hospital discharge challenging. To address this issue, the Drug Enforcement Administration (DEA) granted an exception allowing hospitals, clinics, and EDs to dispense a 72-hour supply of methadone while continued treatment is arranged. Though this exception addresses a critical unmet need, guidance for operationalizing this service is limited. To facilitate expanded patient access to methadone on ED or hospital discharge at 2 Baltimore hospitals, key stakeholders within the parent health system were identified, and a workgroup was formed. Processes were established for requesting, approving, preparing, and dispensing the methadone supply using an electronic health record order set. Multidisciplinary educational materials were created to support end users of the workflow. In the first 3 months of implementation, 42 requests were entered, of which 36 were approved, resulting in 79 dispensed methadone doses. CONCLUSION: This project demonstrates feasibility of methadone dispensing at hospital and ED discharge. Further work is needed to evaluate impact on patient outcomes, such as hospital and ED utilization, length of stay, linkage to treatment, and retention in treatment.

Evaluation of opioid use disorder treatment outcomes in patients receiving split daily versus once daily dosing of buprenorphine-naloxone.

INTRODUCTION: In clinical practice, sublingual (SL) buprenorphine-naloxone is prescribed as once daily or split daily dosing for the management of opioid use disorder (OUD). Evidence is lacking that assesses how split daily buprenorphine-naloxone affects OUD outcomes. This study aims to evaluate how the dosing frequency of SL buprenorphine-naloxone impacts therapy effectiveness when treating patients with OUD. METHODS: This retrospective analysis included adult outpatients prescribed treatment with SL buprenorphine-naloxone for OUD between July 1, 2016, and March 1, 2020. The study excluded patients with sickle cell disease, recent methadone treatment, or pregnancy. We characterized study groups by dosing frequency, either once daily or split dosing. The study compared retention in treatment, medication adherence, adherence to treatment program, and hospital encounters between groups. RESULTS: The study screened eight-hundred and seven patients, and included 250 patients newly prescribed SL buprenorphine-naloxone. Fifty-seven patients (22.8 %) were prescribed once daily dosing and 193 patients (77.2 %) were prescribed split daily dosing. The study found no significant differences noted in 12-month rates of treatment retention (52.6 % vs. 45.6 %, p = .35). These outcomes remained similar when assessed at three and six months. Within a year of buprenorphine-naloxone initiation, the study found no differences in the percentage of patients with hospitalizations (26.3 % vs. 38.3 %, p = .10), median number of hospitalizations (2 vs. 2), or proportion of days covered by a prescription ≥80 % (93.3 % vs. 92.0 %, p = .82). CONCLUSIONS: In this study, patients receiving once daily buprenorphine-naloxone had similar treatment outcomes to patients receiving split dosing. Further controlled studies are necessary to evaluate which patients are more likely to benefit from split dosing.

Adult cancer pain.

Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain.

Prevention of Steroid-Induced Neuropsychiatric Complications With Neuroleptic Drugs: A Review.

Corticosteroids are used for a multitude of indications in palliative patients. In this narrative review, we aim to review literature on the treatment and prevention of neuropsychiatric complications of steroids. For prevention, only lamotrigine had a positive effect in a small number of studies. For treatment, olanzapine appears to be nearly universally effective at low doses, but randomized trial evidence is lacking. Further randomized clinical trials are necessary to elucidate data-driven guidelines for prevention and treatment of corticosteroid-induced neuropsychiatric symptoms. Until further data are available, it is reasonable to consider low dose olanzapine for any patient taking 40 mg of prednisone or its equivalent, especially those with a history of depression or neuropsychiatric symptoms.

A new program in pain medicine for medical students: integrating core curriculum knowledge with emotional and reflective development.

OBJECTIVE: Improvements in clinical pain care have not matched advances in scientific knowledge, and innovations in medical education are needed. Several streams of evidence indicate that pain education needs to address both the affective and cognitive dimensions of pain. Our aim was to design and deliver a new course in pain establishing foundation-level knowledge while comprehensively addressing the emotional development needs in this area. SETTING: One hundred eighteen first-year medical students at Johns Hopkins School of Medicine. OUTCOME MEASURES: Performance was measured by multiple-choice tests of pain knowledge, attendance, reflective pain portfolios, and satisfaction measures. RESULTS: Domains of competence in pain knowledge included central and peripheral pain signalling, pharmacological management of pain with standard analgesic medications, neuromodulating agents, and opioids; cancer pain, musculoskeletal pain, nociceptive, inflammatory, neuropathic, geriatric, and pediatric pain. Socio-emotional development (portfolio) work focused on increasing awareness of pain affect in self and others, and on enhancing the commitment to excellence in pain care. Reflections included observations on a brief pain experience (cold pressor test), the multidimensionality of pain, the role of empathy and compassion in medical care, the positive characteristics of pain-care role models, the complex feelings engendered by pain and addiction including frustration and disappointment, and aspirations and commitments in clinical medicine. The students completing feedback expressed high levels of interest in pain medicine as a result of the course. DISCUSSION: We conclude that a 4-day pain course incorporating sessions with pain specialists, pain medicine knowledge, and design-built elements to strengthen emotional skills is an effective educational approach. SUMMARY: Innovations in medical education about pain are needed. Our aim was to design and deliver a new course for medical students addressing both the affective and cognitive dimensions of pain. Combining small-group sessions with pain specialists, active-learning approaches to pain knowledge, and design-built elements to strengthen emotional skills was highly effective.

Perioperative methadone prescribing and association with respiratory depression.

OBJECTIVE: Over 80 percent of surgery patients experience acute post-operative pain and less than half feel their pain is adequately controlled. Patients receiving chronic opioids, including methadone, are at the highest risk of inadequate pain control. Guidelines do not provide specific recommendations for analgesia management in this population. The purpose of this study was to evaluate the association between post-operative methadone use and respiratory depression. DESIGN: This study was a single center, retrospective, cohort study of adult patients. SETTING: Patients included were admitted to a single academic medical center from July 2016 to September 2018. PARTICIPANTS: Medical records of adult inpatients with an operative procedure who received perioperative methadone were reviewed. MAIN OUTCOME MEASURES: Preoperative methadone use was evaluated for all patients. Post-operative methadone dosing was compared to preoperative methadone dosing. Post-operative respiratory depression was evaluated. Logistic regression was performed to identify risk factors for respiratory depression. RESULTS: Two hundred ninety-eight patients were included in the study. Patients were divided into groups based on pre-operative methadone use. Over 90 percent of patients were on preoperative methadone. There were no significant differences in baseline characteristics between groups. In the initial seven post-operative days, 14.8 percent of patients had documented respiratory depression. Respiratory depression was more common among patients who were newly initiated on methadone post-operatively. Factors associated with respiratory depression included male sex, increased age, and new post-operative methadone initiation. CONCLUSIONS: Most patients who were administered post-operative methadone were on preoperative methadone. New post-operative methadone initiation was a risk factor for respiratory depression.

Current state of opioid stewardship.

PURPOSE: The opioid epidemic continues to result in significant morbidity and mortality even within hospitals where opioids are the second most common cause of adverse events. Opioid stewardship represents one model for hospitals to promote safe and rational prescribing of opioids to mitigate preventable adverse events in alliance with new Joint Commission standards. The purpose of this study was to identify the prevalence of current hospital practices to improve opioid use. METHODS: A cross-sectional survey of hospital best practices for opioid use was electronically distributed via electronic listservs in March 2018 to examine the presence of an opioid stewardship program and related practices, including formulary restrictions, specialist involvement for high-risk patients, types of risk factors screened, and educational activities. RESULTS: Among 133 included hospitals, 23% reported a stewardship program and 14% reported a prospective screening process to identify patients at high risk of opioid-related adverse events (ORAEs). Among those with a prospective screening process, there was variability in ORAE risk factor screening. Formulary restrictions were dependent on specific opioids and formulations. Patient-controlled analgesia was restricted at 45% of hospitals. Most hospitals reported having a pain management service (90%) and a palliative care service providing pain management (67%). CONCLUSION: The absence of opioid stewardship and prospectively screening ORAEs represents a gap in current practice at surveyed hospitals. Hospitals have an opportunity to implement and refine best practices such as access to pain management specialists, use of formulary restrictions, and retrospective and prospective monitoring of adverse events to improve opioid use.

Optimizing opioid prescribing and pain treatment for surgery: Review and conceptual framework.

PURPOSE: Millions of Americans who undergo surgical procedures receive opioid prescriptions as they return home. While some derive great benefit from these medicines, others experience adverse events, convert to chronic opioid use, or have unused medicines that serve as a reservoir for potential nonmedical use. Our aim was to investigate concepts and methods relevant to optimal opioid prescribing and pain treatment in the perioperative period. METHODS: We reviewed existing literature for trials on factors that influence opioid prescribing and optimization of pain treatment for surgical procedures and generated a conceptual framework to guide future quality, safety, and research efforts. RESULTS: Opioid prescribing and pain treatment after discharge from surgery broadly consist of 3 key interacting perspectives, including those of the patient, the perioperative team, and, serving in an essential role for all patients, the pharmacist. Systems-based factors, ranging from the organizational environment's ability to provide multimodal analgesia and participation in enhanced recovery after surgery programs to other healthcare system and macro-level trends, shape these interactions and influence opioid-related safety outcomes. CONCLUSIONS: The severity and persistence of the opioid crisis underscore the urgent need for interventions to improve postoperative prescription opioid use in the United States. Such interventions are likely to be most effective, with the fewest unintended consequences, if based on sound evidence and built on multidisciplinary efforts that include pharmacists, nurses, surgeons, anesthesiologists, and the patient. Future studies have the potential to identify the optimal amount to prescribe, improve patient-focused safety and quality outcomes, and help curb the oversupply of opioids that contributes to the most pressing public health crisis of our time.

Non-pharmacologic treatments for symptoms of diabetic peripheral neuropathy: a systematic review.

Objective: To systematically assess benefits and harm of non-pharmacologic interventions for diabetic peripheral neuropathy (DPN) symptoms.Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life).Results: Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias.Conclusions: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.

Development and implementation of procedures for outpatient naloxone prescribing at a large academic medical center.

PURPOSE: An interprofessional initiative to operationalize outpatient naloxone prescribing at a large academic medical center is described. SUMMARY: The initiative was carried out by a work group of clinical pharmacists and pharmacy administrators in collaboration with physicians and nursing staff leaders from multiple practice settings. An opioid overdose risk-assessment guide was developed on the basis of literature review and expert opinion. An institutional policy to guide identification of high-risk patient populations and facilitate naloxone prescribing and dispensing was developed and vetted by multiple expert committees. Patient education materials were created, and patients at high risk for opioid overdose were educated about overdose risk factors and naloxone use by a pharmacist and/or nurse before discharge or, in some cases, by outpatient pharmacists; when feasible, patients' friends, family members, and/or caregivers were included in education sessions. Interventions included distribution of a pamphlet emphasizing the importance of contacting emergency medical services personnel immediately in the event of an overdose, depicting the process for administration of injectable and nasal spray formulations of naloxone, and providing information on other first-response steps. Collaboration with outpatient pharmacies allowed for successful dispensing of naloxone prescriptions. CONCLUSION: The implementation of an outpatient naloxone prescribing policy at a large academic medical center created a streamlined approach for the interprofessional healthcare team to use in providing naloxone education and improved naloxone access to patients at high risk for opioid overdose.

Pharmacotherapy for diabetic peripheral neuropathy pain and quality of life: A systematic review.

OBJECTIVE: To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life. METHODS: We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE). RESULTS: We updated a recently completed systematic review of 57 eligible studies with 24 additional published studies and 25 unpublished studies. For reducing neuropathy-related pain, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo. We could not draw conclusions about quality of life due to incomplete reporting. All studies were short-term (less than 6 months), and all effective drugs had more than 9% dropouts from adverse effects. CONCLUSIONS: For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo. However, quality of life was poorly reported, studies were short-term, drugs had substantial dropout rates, and opioids have significant risks. Future studies should evaluate longer-term outcomes, use methods and measures recommended by pain organizations, and assess patients' quality of life.

Cancer pain management in the 21st century.

Cancer causes pain as it invades bone, compresses nerves, produces obstructive symptoms in the pulmonary, gastrointestinal, and genitourinary systems, and distends involved visceral organs. This manuscript reviews progress in cancer pain management during the past 2 decades. Since the 1980s, we have seen (1) genuine advances in research on the biology of pain, (2) new approaches to the treatment of cancer pain, and (3) important changes in the health-care system to ensure that pain is appropriately assessed and managed. Currently, clinicians have the appropriate diagnostic and therapeutic tools to ensure that the vast majority of patients with cancer pain can be comfortable during their illness. Nevertheless, too many patients with terminal malignancies continue to die in pain in nations around the globe. An effective strategy to make alleviating pain a major health-care priority remains the primary challenge to effectively palliating patients with cancer pain.

Equianalgesic dosing of opioids.

The concept of opioid equianalgesia, limitations in current dose conversion systems, equianalgesic dose tables, and computer assisted dose conversions are discussed. Conversions for methadone, fentanyl and hydromorphone are described.

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

Team Leadership and Cancer End-of-Life Decision Making.

End-of-life decision making in cancer can be a complicated process. Patients and families encounter multiple providers throughout their cancer care. When the efforts of these providers are not well coordinated in teams, opportunities for high-quality, longitudinal goals of care discussions can be missed. This article reviews the case of a 55-year-old man with lung cancer, illustrating the barriers and missed opportunities for end-of-life decision making in his care through the lens of team leadership, a key principle in the science of teams. The challenges demonstrated in this case reflect the importance of the four functions of team leadership: information search and structuring, information use in problem solving, managing personnel resources, and managing material resources. Engaging in shared leadership of these four functions can help care providers improve their interactions with patients and families concerning end-of-life care decision making. This shared leadership can also produce a cohesive care plan that benefits from the expertise of the range of available providers while reflecting patient needs and preferences. Clinicians and researchers should consider the roles of team leadership functions and shared leadership in improving patient care when developing and studying models of cancer care delivery.